Biocompatible optically transparent polymeric material based upon collagen and method of making

ABSTRACT

The present invention is biocompatible polymer containing the copolymerization product of a mixture of hydrophobic and hydrophilic acrylic and/or allelic monomers, graft-polymerized with telo-collagen. The present material is useful in the production of deformable lenses, for example, intraocular lenses, refractive intraocular contact lenses, and standard contact lenses useful, for example, for correcting aphekia, myopia and hypermetropia.

RELATED APPLICATION

This application is a continuation-in-part application of U.S. patentapplication Ser. No. 08/279,303, filed Jul. 22, 1994, now abandoned,which application is incorporated by reference in its entirety.

FIELD OF THE INVENTION

This invention relates to a biocompatible polymer containing thecopolymerization product of a mixture of hydrophobic and hydrophilicacrylic and/or allelic monomers, and telo-collagen preliminarilypurified from glucoproteins and proteoglucanes. The material is usefulfor the production of soft intraocular lenses, refractive intraocularcontact lenses, and standard contact lenses useful for example, incorrecting aphekia, myopia and hypermetropia.

BACKGROUND OF THE INVENTION

Ordinary polymers, based upon pure non-polyenic acrylates or allelicmonomers, do not have on their surfaces water-solvent ionic layers ontheir surfaces which are buffered against the sorption of proteins.Providing water-solvent ionic layers on the surface of the polymer isdesirable because such layers will greatly improve the bio-compatibilityof the lens with cell membranes of the recipient's eye.

Polyenic water-solvent ionic monomers may be used in order to produce awater-solvent layer. However, this decreases the resistance of suchcopolymers against swelling. For example, the system of polyeniccopolymers, based upon acrylamid or acrylic acid with HEMA has atendency towards excessive swelling beyond all bounds. This happensbecause pure homopolymers, polyacrylamide or polyacrylic acid, containedin this system, dissolve in water. Therefore, it is an advantage toproduce a polymer which would be able to form such a vital water-solventlayer, and would not affect the polymer resistance against swelling.

References concerning graft-copolymers of collagen include U.S. Pat. No.4,388,428 Jun. 14, 1983) and U.S. Pat. No. 4,452,925 (Jun. 5, 1994). Inthese patents, a system of water-soluble monomers and A telo-collagen isused. However, this system is not hydrolytically stable and is notsufficiently optically transparent. In U.S. Pat. No. 4,452,925, nothingis mentioned of special optical conditions needed for transparentpolymer production. The water-solvent A telo-collagen disclosed in thispatent does not have the capacity to form a gel in the organic monomersolution, and therefore the collagen precipitates or coagulates.

SUMMARY OF THE INVENTION

An object of the present invention is to provide a biocompatibleoptically transparent polymeric material based on telo-collagen.

A further object of the present invention is to provide a biocompatiblepolymer containing the copolymerization product of a mixture ofhydrophobic and hydrophilic acrylic and/or allelic type-monomers andtelo-collagen.

An object of the present invention is to provide a method of making abiocompatible, optically transparent, polymeric material based oncollagen.

A further object of the present invention is to provide a method ofmaking a biocompatible polymer containing the copolymerization productof a mixture of hydrophobic and hydrophilic acrylic and/or allelictype-monomers and telo-collagen.

The present invention is directed to methods of making a biocompatiblepolymeric material based on collagen for use in the production ofdeformable lenses.

The present invention is also directed to an deformable lens comprisedof the present optically transparent, biocompatible, polymeric material.

The present invention is further directed to methods for makingdeformable lenses.

The present invention is also directed to methods for correcting aphekia(absence of the lens of the eye), myopia or hypermetropia in a patientby surgically implanting in the eye of the patient, the presentdeformable lens.

The biocompatible polymeric material according to the present inventionis made as a copolymerization product of a mixture of hydrophobic andhydrophilic acrylic and/or allelic monomers graft polymerized withtelo-collagen. For example, one or more hydrophobic acrylic and/orallelic monomers are mixed with one or more hydrophilic acrylic and/orallelic monomers, and the resultant solution is then mixed withtelo-collagen dissolved in one or more hydrophilic acrylic and/orallelic monomers. The resulting material is then irradiated to form thepresent biocompatible optically transparent polymeric material.

The telo-collagen used in the present invention is essentially type IVcollagen obtained from pig's eye sclera or cornea. The collagen is anaturally stable polyenic, which comprises hydrophobic, hydroxylic andpolarized amino-acids (Matsumura, T., Relationship Between Amino-AcidComposition and Differentiation of Collagen, Lut. J. Biochem.3(15):265-274 (1972), and Traub W., and Piez K. A., The Chemistry andStructure of Collagen, Advances in Protein Chem 25:243-352, (1971). Itis not advisable to use a modified collagen in the system according tothe present invention since this collagen biodegrades with time (U.S.Pat. No. 4,978,352, Dec. 18, 1990).

The resulting biocompatible polymeric material is an elastic biopolymer,based upon the mixture of the hydrophobic and hydrophilic monomers andtelo-collagen. The product of the hydrophobic and hydrophilic monomercopolymerization exhibits an elevated hydrolytic stability and a muchhigher index of refraction, if compared with a polymer which is basedupon hydrophilic monomers alone.

The high molecular mass of telo-collagen molecules (320,000 D), theirsize (up to 1000 A), the disorientation of molecules in space, therefraction index 1.47 (Hogan J. J. et. al., Histology of Human Eyes, AnAtlas and Textbook, Philadelphia, London, Toronto, (1971)), and othercharacteristics of collagen make it impossible to produce opticallytransparent hydrogel implants made of collagen alone. The refractionindex of the hydrogel base substance, the aqueous number is equal to1.336, which is substantially different from the refractive index ofcollagen 1.47, resulting in opacification of the gel, if a suspension ofcollagen in aqueous monomer is made.

In order to produce an optically homogeneous gel in the mixture oforganic monomers it is necessary to utilize telo-collagen containingtelo-peptide. Telo-peptide is the basic element of interaction amongcollagen molecules. This produces a stable gel in the mixture ofhydrophobic and hydrophilic monomers, and this gel neither precipitatesnor coagulates.

For the purpose of increasing the optical transparency and homogeneityin this system, the refraction index of polymer and of telo-collagenshould be approximately equal, so that the intensity of light diffusionis close to zero, in accordance with Reley's equation (U. G. Frolof,Course of Colidle Chemistry, Moskva Chemia, 1989): ##EQU1## I_(o) =isintensity of incident light; I=is the intensity of diffused light as aunit of radiation volume;

P_(r) =distance to detector;

w=light diffusion angle;

C=concentration of particles per volume unit;

λ=length of incident light wave;

N₁ =refraction index of particles;

N_(o) =refraction index of basal substance; and

V=volume of particles.

If N₁ =N_(o), then I_(p) =O. Thus, the intensity of light diffusion iszero.

A preferred hydrophilic acrylic monomer for use in the present inventionis 2-hydroxyethyl methacrylate (HEMA), and a preferred hydrophobicmonomer for use in the present invention is4-metharyloxy-2-hydroxybenzophenone. The telo-collagen is preferablyproduced from pig's eye sclera or cornea.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

I. Definitions:

The below definitions serve to provide a clear and consistentunderstanding of the specification and claims, including the scope to begiven such terms.

Telo-collagen. By the term "telo-collagen" is intended for the purposesof this invention a naturally stable polyenic, that containshydrophobic, hydroxylic and polarized amino-acids (Matsumura, T.,Relationship Between Amino-Acid Composition and Differentiation ofCollagen Lut. J. Biochem 3(15):265-274 (1972).

The present telo-collagen is essentially type IV telo-collagenpreferably made from pig's eye sclera or cornea, and has a viscosity ofgreater than or equal to 1000 cPs. The present telo-collagen retains thetelo-peptides and has a refractive index of about 1.44 to 1.48.

Biocompatible polymeric material. By the terminology "biocompatiblepolymeric material" is intended a material which is made by combining ormixing one or more hydrophobic monomers (acrylic and/or allelicmonomers), and one or more hydrophilic monomers (acrylic and/or allelicmonomers), and graft-copolymerizing the resultant mixture with atelo-collagen/hydrophilic monomer/acid solution.

Monomer. By the term "monomer" denotes the molecular unit that byrepetition, constitutes a large structure or polymer. For exampleethylene CH₂ ═CH₂ is the monomer of polyethylene, H(CH₂)NH.

Allyl. By the term "allyl" is intended 2-propenyl, the monovalentradical, CH₂ ═CHCH₂ --.

Organic Acid. By the term "organic acid" is intended an acid made up ofmolecules containing organic radicals. Such acids include for example,formic acid (H--COOH), acetic acid (CH₃ COOH) and citric acid (C₆ H₈O₇), all of which contain the ionizable --COOH group.

Acrylic. By the term "acrylic" is intended synthetic plastic resinsderived from acrylic acids.

Optically Transparent. By the terminology "optically transparent" isintended the property of a polymeric material to allow the passage oflight at or above the threshold of visual sensation (i.e., the minimumamount of light intensity invoking a visual sensation). Preferably, thepresent biocompatible polymeric material including COLLAMER has arefractive index in the range of 1.44 to 1.48, more preferably 1.45 to1.47, and most preferably 1.45 to 1.46. The best mode of the presentinvention is the biocompatible polymeric material COLLAMER.

Polymerization. By the term "polymerization" is intended a process inwhich monomers combine to form polymers. Such polymerization can include"addition polymerization" where monomers combine and no other productsare produced, and "condensation polymerization" where a by-product (e.g.water) is also formed. Known suitable polymerization processes can bereadily selected and employed for the production of the presentbiocompatible polymeric material by those of ordinary skill in the artto which the present invention pertains.

Polyene. By the term "polyene" is intended a chemical compound having aseries of conjugated (alternating) double bonds, e.g., the carotenoids.

Refractive Index. By the terminology "refractive index" is intended ameasurement of the degree of refraction in translucent/transparentsubstances, especially the ocular media. The "refractive index" ismeasured as the relative velocity of fight in another medium (such asthe present polymeric material) as compared to the velocity of light inair. For example, in the case of air to crown glass the refractiveindex(n) is 1.52, in the case of air to water n=1.33.

Tensile Strength. By the terminology "tensile strength" is intended themaximal stress or load that a material is capable of sustainingexpressed in kPa. The present biocompatible polymeric material includingCOLLAMER has a tensile strength in the range of about 391-1778 kPa,preferably 591-1578 kPa, more preferably 791-1378 kPa, and mostpreferably in the range of from 991 kPa to 1178 kPa. The presentmaterial "COLLAMER" has a tensile strength of preferably 1085±493 kPa.The tensile strength of a polymeric material can be readily determinedusing known methods, by those of ordinary skill in the art.

Hypermetropia. By the term "hypermetropia" (h.) is intendedfarsightedness/longsightedness, i.e., long or far sight which is anoptical condition in which only convergent rays can be brought to focuson the retina. Such conditions include: (1) absolute h.--that cannot beovercome by an effort of accommodation; (2) axial h.--h. that is due toshortening of the anteroposterior diameter of the globe of the eye; (3)curvature h.--h. which is due to the decreased refraction of theanterior diameter of the globe of the eye; (4) manifest.--h. that can becompensated by accommodation; (5) facultative h.--manifest h.; (6)latent h.--the difference between total and manifest h.; and (7) totalh.--that which can be determined after complete paralysis ofaccommodation by means of a cycloplegic; (8) index h.--h. arising fromdecreased refractivity of the lens.

Myopia. By the term "myopia" (m) is intended "shortsightedness;nearsightedness; near or short sight; that optical condition in whichonly rays a finite distance from the eye focus on the retina. Suchconditions include: (1) axial m.--m. due to elongation of the globe ofthe eye; (2) curvature.--m. due to refractive errors resulting fromexcessive corneal curvature; (3) degenerative.--pathologic m.; (4) indexm.--m. arising from increased refractivity of the lens, as in nuclearsclerosis; (5) malignant.--pathologic m.; (6) night.--m. occurring in anormally emmetropic eye because long light rays focus in front of theretina; (7) pathologic.--degenerative or malignant., progressive. markedby fundus changes, posterior staphyloma and subnormal corrected acuity;(8) prematurity m.,.--m. observed in infants of low birth weight or inassociation with retrolental fibroplasia; (9) senile lenticular.--secondsight; (10) simple m.--m. arising from failure of correlation of therefractive power of the anterior segment and the length of the eyeball;(11) space.--a type of m. arising when no contour is imaged on theretina; and (12) transient.--m. observed in accommodative spasmsecondary to iridocyclitis or ocular contusion.

Hydrophilic allelic monomer. By the term "hydrophilic allelic monomer"is intended for the purposes of the present invention any monomercontaining an allyl group which monomer is soluble in water.

Hydrophilic acrylic monomer. By the terminology "hydrophilic acrylicmonomer" is intended any monomer containing an acrylic group whichmonomer is soluble in water. For example, HEMA is a hydrophilic acrylicmonomer because it is soluble in water even though it contains bothhydrophilic groups and hydrophobic groups.

Hydrophobic allelic monomer. By the term "hydrophobic allelic monomer"is intended for the purposes of the present invention, any monomercontaining an allyl group, which monomer is not soluble in water.

Hydrophobic acrylic monomer. By the term "hydrophobic acrylic monomer"is intended for the purposes of the present invention, any monomercontaining an acrylic group, which monomer is not soluble in water.

Deformable lens. By the term "deformable lens" is intended any type ofdeformable lens, for example, for correcting hypermetropia or myopia,where the lens comprises the present material. Such lenses include thosedisclosed in U.S. patent application Ser. Nos. 08/318,991 and08/225,060. All of the foregoing are hereby incorporated by referenceherein. Such lenses include: intraocular lenses for implantation into apatient's eye, for example, into the anterior chamber, in the bag or inthe sulcas; refractive intraocular lenses for implantation into apatient's eye, for example, into the anterior chamber or in the sulcas;and standard soft contact lenses.

Implant. By the term "implant" is intended the surgical method ofintroducing the present lens into the eye of a patient, for example,into the anterior chamber, in the bag or in the sulcas, by the methodsdescribed in U.S. patent application Ser. Nos. 08/195,717, 08/318,991,and 08/220,999 using for example, surgical devices disclosed in U.S.patent application Ser. Nos. 08/197,604, 08/196,855, 08/345,360, and08/221,013. All of the foregoing are hereby incorporated by reference.

The present hydrophilic monomers and hydrophobic monomers must beselected such that the hydrophobic monomer(s) is soluble in thehydrophilic monomer(s). The hydrophilic monomer acts as a solvent forthe hydrophobic monomer. Suitable monomers can be readily selected bythose of ordinary skill in the art to which the present inventionpertains.

Examples of suitable hydrophobic monomers, include:

1) 4-methacryloxy-2-hydroxybenzophenone (acrylic);

2) ethyl-3 benzoil acrylate (acrylic);

3) 3-allyl-4-hydroxyacetophenone (allelic);

4) 2-(2'-hydroxy-3'-allyl-5'-methylphenyl)-2H-benzotriazole (allelic);

5) N-propyl methacrylate (acrylic);

6) allyl benzene (allelic);

7) allyl butyrate (allelic);

8) allylanisole (allelic);

9) N-propyl methacrylate (acrylic);

10) ethyl- methacrylate (acrylic);

11) methyl methacrylate (acrylic);

12) n-heptyl methacrylate (acrylic).

Various examples of suitable hydrophilic monomers, include:

1) 2-hydroxyethyl methacrylate (HEMA) (acrylic);

2) hydroxypropyl methacrylate (acrylic);

3) 2-hydroxyethyl methacrylate (acrylic);

4) hydroxypropyl methacrylate (acrylic);

5) allyl alcohol (allelic);

6) poly(ethylene glycol)n monomethacrylate (acrylic);

7) 4-hydroxybutyl methacrylate (acrylic);

8) allyl glucol carbonate (allelic).

II. Method of Making the Present Polymeric Material Based on Collagen

The following is a description of a preferred method of making thebiocompatible polymeric material according to the present invention.

Step 1:

The hydrophilic monomer is mixed with an acid, in particular formicacid. The weight ratio of hydrophilic monomer to acid is preferably inthe range of about 5:1 to about 50:1, preferably 14:1 to 20:1, and mostpreferably, 14:1. This solution is preferably filtered through a 0.2microfilter.

Step 2:

In an independent step, an acidic telo-collagen solution is prepared bymixing telo-collagen with organic acid (preferably formic acid). Thesolution is preferably 2% by weight telo-collagen in 1M formic acid.

Step 3:

The solutions resulting from steps 1 and 2 are then mixed together. Theresultant solution is preferably mixed from about 10 minutes to 60minutes, most preferably 20 minutes at a temperature of 15°-30° C. Theratio of telo-collagen to hydrophilic monomer is about 1:2 to about 1:7,preferably 1:3 to 1:6, and most preferably 1:4.

Step 4:

In an independent step, the hydrophobic monomer and hydrophilic monomerare mixed together in a weight ratio of about 10:1 to 1:1, preferably8:1 to 3:1, and most preferably 5:1. The monomers are mixed withstirring for about 30 to 90 minutes, preferably 60 minutes at 70° to 95°C., preferably 80°-95° C., and most preferably 80°-92° C. The resultingsolution is preferably filtered through a 0.2 micron filter.

Step 5:

The solutions from steps 3 and 4 are mixed together in a weight ratio inthe range of about 1:1 to 50:1, preferably 2:1 to 5:1, and mostpreferably 3:1. The solution is preferably mixed 20 minutes with noheating at a temperature of 25°-40° C. Mixing is preferably performedwith a homogenizer.

Step 6:

The resulting material from Step 5 is then preferably degassed (i.e.,using centrifugation or other means well-known to those of ordinaryskill in the art to which the present invention applies).

Step 7:

The resulting material from Step 6 is irradiated to form a final productthat can be dried, and stored, (i.e., stored in a desiccator due to itshydroscopic nature). The material from Step 6 can also be stored in arefrigerator, for example at 5° C. to 10° C., prior to irradiation.

A polymeric material according to the present invention is obtained froman interaction between a solution of telo-collagen complex, and thehydrophilic and the hydrophobic monomers under radiation of 1 Mrad/hrfor a total dose of from 0.20 to 0.80 Mrad, preferably 0.30 to 0.60Mrad, and most preferably from 0.35 to 0.50 Mrad (1 Mrad=10 Kgray).

A turbo-type mixer such as a homogenizer, is preferably employed formixing the solutions of at least Steps 3 and 5, and the mixing times setforth above are based on using a turbo-type mixer. Those of ordinaryskill in the art can readily select and employ other known mixers andmethods, as well as time ranges.

In a preferred embodiment the present polymeric material is made bymixing the hydrophobic monomer in two stages to increase the solutionviscosity, where in stage one the telo-collagen complex and a mixture offormic acid with 2-hydroxyethyl-methacrylate are used as a stabilizer ofultra-colloidal state solution and in stage two a hydrophobic blend ofat least one monomer is introduced into the gel produced.

III. Standardized Method for the Compounding of the present COLLAMER

A. Preparation of Acidic Collagen Solution

A 1M acid solution, preferably 1M formic acid is prepared. The quantityof acid solution required for dissolution of the swollen tissue iscalculated using a ratio of swollen collagen tissue: (sclera or cornea)acid solution of about 40:0.5 to 55:2, preferably about 45:1 to about52:1.5, most preferably about 50:1.

The swollen tissue is then dispensed in a homogenizer for about 10 to 20minutes, preferably about 15 minutes at 2 to 10 RPM, preferably 4-5 RPM,at room temperature. The produced solution is then filtered through afunnel glass filter with a pore size of 100-150 microns, the filtrate isthen filtered through a second funnel glass filter with a pore size of5-100 microns. The produced homogenic solution is then transferred intoa container.

B. Hydrophobic and Hydrophilic Solution Preparation

1. The hydrophilic monomer, preferably HEMA is mixed with thehydrophobic monomer, preferably MHBPH in a weight ratio of about 5:1 andheated for one hour at 80° C. to 92° C. with stirring (e.g., using astirrer hot plate). The heated solution is then filtered through 5.0micron filter.

2. HEMA is mixed with an organic acid (preferably formic acid),preferably in a weight ratio of about 14:1. This mixture is added to thecollagen solution produced (A) in a weight ratio of HEMAsolution:collagen solution of about 1:3, and mixed for about 20 minutesat room temperature. The mixing is preferably performed using ahomogenizer at a rate of 6000 RPM.

3. The HEMA MHBPH solution of B.(1) is then mixed in small portions withthe HEMA telo-collagen solution of B.(2). The mixing is preferablyperformed in a homogenizer for 10 minutes at room temperature.

C. Production of COLLAMER

Glass vials are then coated with approximately 7 mm of paraffin wax. Thesolution of B(3) is then poured into the glass vials and degassed (e.g.,centrifuged for 15 minutes to remove air). The vials are subsequentlyirradiated at 5 Kgray. (Note: prior to irradiation the vials can bestored in a refrigerator, for example at 5° C. to 10° C.)

IV. Guidance for Selecting the Present Monomers

The following equation can be used to aid in the selection of theappropriate concentration of monomer necessary to result in the presentpolymeric material having an index of refraction in the present desiredrange (1.44 to 1.48, preferably 1.45 to 1.47, and most preferably 1.45to 1.46).

The monomer of copolymerization with telo-collagen complex is selectedsuch that:

N=(K_(s) ·N_(a))+(1-K_(s))N_(p) =N_(c) ±0.02

K_(s) =coefficient of swelling

N_(a) =refractive index of water (1.336)

N_(p) =refractive index of dry polymer

N_(c) =refractive index of telo-collagen (about 1.45 to 1.46)

where ##EQU2## N_(i) =refractive index of i-monomer C_(i) =concentrationof i-monomer

A=coefficient of increase in refractive index due to polymerization

n=number of monomers

i=monomer number

The hydrophobic and hydrophilic monomers must be selected such that thehydrophilic monomer is a solvent for the hydrophobic monomer, i.e., thehydrophobic monomer is soluble in the hydrophilic monomer.

The manner and method of carrying out the present invention may be morefully understood by those of skill in the art to which the presentinvention pertains by reference to the following examples, whichexamples are not intended in any manner to limit the scope of thepresent invention or of the claims directed thereto.

EXAMPLES Example I

Compounding COLLAMER

A. Preparation of acidic collagen solution

Under an exhaust hood, 1 liter of distilled water was measured into a 3liter glass beaker. 52 grams of formic acid was then added to the beakerand mixed until dissolved. Swollen collagen containing tissue (frompig's eyes) was then added to the acid solution in the below ratios ofswollen tissue:acid solution.

    ______________________________________                                        Swollen Tissue    Acid Solution                                               ______________________________________                                        1.      517.00 grams  10.21 grams                                             2.      50.64 grams   1.00 grams                                              ______________________________________                                    

The mixture was then stored in a refrigerator at a temperature of 5° C.,and was thereafter dispersed in a homogenizer for 15 minutes at 4-5 RPMat room temperature.

The produced solution was then filtered through a funnel glass filterwith a pore size of 100-150 microns. Thereafter, the filtrate wasfiltered through a funnel glass filter with a pore size of 75-100microns. The final homogenic solution was then transferred into a 250 mlcontainer.

B. MHBPH and HEMA solution preparation

1. 527.4 g of HEMA was mixed with 106.2 g of MHBPH and heated for onehour at 80° C. using a stirrer hot plate. The heated solution wasfiltered through an Acro 50-5.0 micron filter.

2. 1415.6 g of HEMA was then mixed with 99.4 g of formic acid in ahermetic glass container with a Teflon lid. 100 g portions of theHEMA/acid solution were added into 333 g of telo-collagen solution andmixed for 20 minutes at room temperature. The mixing was performed in ahomogenizer at a rate of 6000 RPM.

3. The HEMA/MHBPH solution was then added in small portions to the HEMAtelo-collagen solution. The mixing was performed in a homogenizer for 10minutes at room temperature.

C. Production of COLLAMER

Glass vials were coated with approximately 7 mm of paraffin wax. Theresultant solution of Step B(3) was then poured into the glass vials andcentrifuged for 15 minutes to remove air. The vials were then irradiatedat 5 Kgray to polymerize and cross-link the present material.

Example 2

Preparation of a Biocompatible Polymeric Optically Transparent Material

In this example, pig's eye sclera was used. 300 g of 2-hydroxyethylmethacrylate was mixed with 16 g of formic acid. 50 g of telo-collagenwas filtered purified from sclera using alkaline hydrolysis with 200 gNaOH and 200 g of Na₂ SO₄ in 2.5 liters of water, and filtered through a100 micron filter. The telo-collagen was mixed with 2-hydroxyethylmethacrylate and the formic acid solution containing 2-hydroxyethylmethacrylate. 20 g of 4-methacryloxy-2-hydroxybenzophenone (MHBPH)dissolved in HEMA was then added. This mixture was radiated with gammaradiation in the range of 3.5-5.0 Kgray to polymerize and cross-link allthe components.

Hydrophobic monomers were used in this system to reduce the absorptionof water and swelling of the polymerized material when introduced intothe aqueous media of the eye. In addition, the hydrophobic monomer waschosen so that the refractive index of the resultant polymer increasedto be approximately equal to the refractive index of telo-collagen.

Example 3

The same procedure in Example 2 can be utilized, except the followingmonomers can be substituted:

1) ethyl-3-benzoilacrylate (hydrophobic acrylic monomer), plus

1) 2-hydroxyethyl methacrylate (HEMA), (hydrophilic acrylic monomer).

Example 4

The same procedure in Example 2 can be utilized, except the followingmonomers can be substituted:

1) 3-allyl-4-hydroxyacetophenone (hydrophobic allelic monomer), plus

2) 2-hydroxyethyl methacrylate (HEMA), (hydrophilic acrylic monomer).

Example 5

The same procedure in Example 2 can be utilized, except the followingmonomers can be substituted:

1) 2-(2'-hydroxy-3'-allyl-5'-methylphenyl)-2H-benzotriazole (hydrophobicallelic monomer), plus

2) hydroxypropyl methacrylate, (hydrophilic acrylic monomer).

Example 6

The same procedure in Example 2 can be utilized, except the followingmonomers can be substituted:

1) methyl methacrylate (hydrophobic acrylic monomer), plus

2) hydroxypropyl methacrylate (hydrophilic acrylic monomer).

Example 7

The same procedure in Example 2 can be utilized, except the followingmonomers can be substituted:

1) 2-(2'-hydroxy-3'-allyl-5'-methylphenyl)-2H-benzotriazole (hydrophobicallelic monomer), plus

2) hydroxypropyl methacrylate (hydrophilic acrylic monomer).

Example 8

A. Tensile Strength Testing of COLLAMER Material

The purpose of this test was to determine the tensile properties of thepresent collamer material. This includes tensile strength, Young'smodulus, and percent elongation at failure. The data collected was usedto construct standards for inspection. The tensile test is similar tothe silicone tensile test. The sample geometry is different but thestress fundamentals remain the same.

B. Materials

COLLAMER samples

Instron tensile tester (Model 1122)

forceps

log book

C. Procedure

I. Sample Preparation

a. The dry material samples were cut into rings. The dimensions are:Outside diameter=10±0.1 mm, inside diameter=8±0.1 mm, thickness=1.0±0.01mm. The material was prepared following the procedures used tomanufacture lenses. Lenses were hydrated following MSOP #113AG.

2. Testing

a. The instron tester was set up for tensile specimens, following ESOP202, RMX-3 Slab Pull Test, Rev B. The fixtures were placed into the jawsand the fixtures were brought together so that the top and bottomportion touched, by moving the crosshead up or down. When the fixtureswere touching, there was approximately 8 mm between the two pins. Thiswas the starting position of jaw separation, so the Instron positioncoordinates were set to zero.

b. The load dial was set to 2 kg full scale output, the crosshead speedto 500 mm/min and the chart recorder to 500 mm/min. The chart speedcorresponded to and recorded jaw separation. The chart buttons marked"PEN" and "TIME" were depressed.

c. The wet test sample was removed from its vial and placed so it wasalmost stretched between the two pins. When the sample was in place, the"UP" button on the crosshead control panel was immediately pressed. Thissample was then loaded to failure.

d. When the sample failed, the "STOP" button on the crosshead controlpanel was pressed. The chart buttons marked "PEN" and "TIME" were thendepressed so that they were in the up position. The return on thecrosshead control panel was then pressed to return the crosshead tostarting position.

e. The failure point in the chart was then marked by noting the load atfailure (in kg) and jaw separation.

f. Steps 2a through 2e were repeated until all samples were all tested.

C. Data

Calculation for Ultimate Tensile Strength

    σ=F/A                                                (1)

Where:

σ=Ultimate Tensile Strength, Pascals, (Pa).

F=Force required to break the test specimen, Newtons, (N)

A=Hydrated cross sectional area of specimen, square meters, (m²).

δ=Swell Factor, 1.17

w=width, mm

t=thickness, mm

Given:

F=0.29 kg×9.81 m/s² =2.84N

A=2[δ(w)×δ(t)]=2[(1.17×1.0)×(1.17×1.0)]=2.74 mm²

Conversion from mm² to m² : 2.74 mm² =2.74×10⁻⁶ m²

A=2.74×10⁻⁶ m²

Find:

Ultimate Tensile Strength, σ

Solution:

σ=F/A=2.84N/2.74×10⁻⁶ m² =1038.3 kPa

To convert kPa to psi, multiply by 145.04×10⁻³ 1038.3 kPa×145.04×10⁻³=150.6 psi

σ=1038.3 kPa or σ=150.6 psi

Calculation for Percent Elongation

    δ=200[L/MC.sub.(TS) ]                                (2)

Where:

δ=elongation (specified), percent,

L=increase in jaw separation at specified elongation, (mm), and

MC.sub.(TS) =mean circumference of test specimen, mm,

circumference=λd

Given:

L=41.5 mm

MC.sub.(TS) =(πd₁ +πd₂)/2=(π×10 mm+π×8 mm)/2=28.27 mm

Find:

Elongation, δ

Solution:

δ=200[L/MC.sub.(TS) ]=200[41.5 mm/28.27 mm]=293.6%

δ=293.6%

Calculation for Young's Modulus

    E=Pl/Ae                                                    (3)

Where:

E=Young's Modulus, Pascals, (Pa)

P=Force, Newtons, (N)

l=length of sample, meters (m)

A=Cross Sectional Area, square meters, (m²)

e=Gross Longitudinal Deformation, meters, (m).

Given:

P=0.29 kg×9.81 m/s² =2.84N

l=0.008 m

A=A═2[δ(w)×δ(t)]=2[(1.17×1.0)×(1.17.times.1.0)]=2.74 mm²

Conversion from mm² to m² : 2.74 mm² =2.74×10⁻⁶ m²

A=2.74×10⁻⁶ m²

e=0.0415 m

Find:

Young's Modulus, E

Solution:

E=Pl/Ae=(2.84N×0.008 m)/(0.0415 m×2.74×10⁻⁶ m²)=200.2 kPa

To convert kPa to psi, multiply by 145.04×10⁻³ 199.8 kPa×145.04×10⁻³=29.0 psi

E=199.8 kPa or 29.0 psi

E. Discussion

The Instron was set up and calibrated according to ESOP #202. Thetesting fixtures were brought together so the centerlines were alignedand there was approximately 8 mm between the posts. This was designatedzero and the fixtures returned to this position every time after thetest. Crosshead speed and the chart recorder speed were set to 500mm/min.

The chart recorder was set at zero load and deflection before everytest. The chart recorder recorded kilograms-force load and jawseparation. Load is used to determine the ultimate tensile strength (seeformula 1, Test Data Section), the stress at which the sample fails. Thesample was not set up to test elongation using a standard gage lengthbut a formula in the ASTM D412 standard is used to calculate theelongation (see formula 2, Data Section).

The performance of the specimen proved the material to be elastic andwith the stress increasing at a linear rate until failure. The linearincrease can be one of two things: (1) it is possible the specimens havestress risers on the inside diameter. Stress risers would be caused bythe milling process, because it doesn't have the surface finish of thelathe-turned outer diameter; this may not allow the material to neckdown during the plastic deformation stage of the test. The majority ofthe stress is concentrated on the internal circumference, which loadsthe stress risers more than if they were on the outside circumference;(2) the material may not neck down (plastic deformation) as do otherplastic materials such as Kapton film. It reacts like RMX-3, with thecross sectional area getting smaller as elongation increases, which isindicative of Hooke's law.

The present material showed COLLAMER good resistance to tearpropagation, which would happen at any stress risers. The crosssectional area of the failed part was flat, which was indicative ofelastic failure.

E. Conclusion

The combined data from the present COLLAMER samples gave an averagetensile strength of 1084.6 kilopascals (kPa), and an average elongationof 324.9 percent (%). The tolerance for average tensile strength wascalculated as ±3 times the standard deviation, giving an upper toleranceof 1578 kPa (229 psi) and a lower tolerance of 591 kPa (86 psi). Thetolerance for the elongation is calculated in the same manner. The uppertolerance is 395% elongation and the lower tolerance is calculated as255% elongation. See Appendix 3 for the calculations. The tensilestrength standard is 1085±493 kPa (157±71 psi) and the elongation is325%±70. Young's modulus standard is 189±25 kPa (27±11 psi).

F. References

ASTM D412 Properties of Rubber in Tension

ESOP 202-RMX-3 Slab Pull Test, Rev B.

Mark's Standard Handbook for Mechanical Engineers, Ninth Edition

All references cited are hereby incorporated by reference. Now havingfully described this invention, it will be understood by those of skillin the art that the scope may be performed within a wide and equivalentrange of conditions, parameters, and the like, without affecting thespirit or scope of the invention or of any embodiment thereof.

We claim:
 1. A method for producing a biocompatible, opticallytransparent, polymeric material, comprising:dissolving anacid-telo-collagen solution in one or more hydrophilic monomers to forma collagen/hydrophilic solution; dissolving one or more hydrophobicmonomers in one or more hydrophilic monomers to form ahydrophobic/hydrophilic solution; combining saidtelo-collagen/hydrophilic and said hydrophobic/hydrophilic solution toform a resultant solution; and graft-polymerizing said resultantsolution to form the present biocompatible, optically transparent,polymeric material based on collagen.
 2. The method of claim 1, whereinsaid step of graft-polymerizing comprises irradiating said resultantsolution.
 3. A biocompatible, optically transparent, polymeric materialbased on telo-collagen, comprising:one or more hydrophilic acrylic orallelic monomers, and one or more hydrophobic acrylic and allelicmonomers; and telo-collagen containing telo-peptides, wherein said oneor more hydrophilic acrylic or allelic monomers and said one or morehydrophobic acrylic or allelic monomers, are graft-polymerized with saidtelo-collagen to form a biocompatible, optically transparent, polymericmaterial based on telo-collagen; said material produced by the processcomprising:dissolving an acid-telo-collagen solution in one or morehydrophilic monomers to form a collagen/hydrophilic solution; dissolvingone or more hydrophobic monomers in one or more hydrophilic monomers toform a hydrophobic/hydrophilic solution; combining saidcollagen/hydrophilic and said hydrophobic/hydrophilic solution to form aresultant solution; and graft-polymerizing said resultant solution toform the present biocompatible, optically transparent, polymericmaterial based on telo-collagen.